Longitudinal Association of Remnant Cholesterol With Cognitive Decline Varies by Lipid-Lowering Drugs: A Population-Based Cohort Study

Abstract

BACKGROUND: Although the association between remnant cholesterol (RC) and cognitive impairment has been reported, the association of RC with cognitive decline remains scarce. Also, the role of lipid-lowering therapy in the association is unclear. The study aimed to examine the longitudinal associations of RC with cognitive decline by lipid-lowering drug use during follow-up. METHODS AND RESULTS: The study used data from Wave 2 (2004–2005) to Wave 8 (2016–2017) of the ELSA (English Longitudinal Study of Ageing). Global cognitive functions at baseline (Wave 2) and during the follow-up (Waves 3–8) were assessed by integrating 3 cognitive domains: memory capacity, semantic fluency, and orientation. Multivariate-adjusted linear mixed models were employed to examine the longitudinal associations, with results presented as β (95% CI) in SD/year. Of the 5053 participants ultimately included, 55.4% were female and the mean age (SD) was 65.7 (9.3) years. Per 1 mmol/L increment in RC was significantly associated with a faster rate of cognitive decline (β=−0.010 SD/year [95% CI −0.019 to −0.001]). Furthermore, we observed that association pattern between RC and cognitive decline only in the non-lipid-lowering drug group (β=−0.019 SD/ year [95% CI, −0.031 to −0.007]) but not in the lipid-lowering drug group (β=0.007 SD/year [95% CI, −0.006 to 0.020]), with a significant interaction (P=0.015). Similar findings were observed for the 3 cognitive domains. CONCLUSIONS: Higher baseline RC levels were associated with steeper cognitive decline. The use of lipid-lowering drugs might mitigate this decline. These findings underscore the importance of early RC monitoring and proactive management with lipid-lowering drugs in clinical practice.